Antigen or Antibody? Hepatitis B and Pregnancy image

Antigen or Antibody? Hepatitis B and Pregnancy

Review the latest recommendations with

Katherine S. Kohari, MD, FACOG

Dr. Kohari, a Maternal-Fetal Medicine specialist, is an Assistant Professor and the Medical Director for MFM Outpatient Services in the Department of Obstetrics and Gynecology at the Yale School of Medicine in New Haven, CT

Learning Objectives: Upon completion of this activity, participants should be better able to:

  • Request and interpret testing for Hepatitis B infection in pregnancy
  • Understand implications of Hepatitis B on pregnancy
  • Identify patients who would benefit from treatment for Hepatitis B
  • Counsel patients on neonatal interventions

Contents

The Case

You are reviewing the results of initial prenatal labs sent on your recent new OB patient

  • 24 yo G1P0 @ 8w3d
  • No reported medical issues
  • Hepatitis B surface antibody test was inadvertently drawn and returns positive
    • Patient now calling your office concerned she has Hepatitis B
    • You reassure her that her testing is likely not consistent with a HBV infection, but more testing is required to better determine her Hepatitis B status

Synopsis

Transmission

  • Hepatitis B (HBV) infects >240 million people worldwide
  • Infectious body fluids include saliva, semen, vaginal secretions and blood
    • Commonly transmitted via sexual contact
    • Increased risk with IV drug use
    • May also be contracted via shared use of household items and childcare
  • Vertical transmission
    • 50% of HBV infection worldwide is attributed to perinatal transmission
    • Routine vaccination is not employed in all countries in the world

Gold Standard of Screening in Pregnancy: Hepatitis B Surface Antigen

  • HBV testing is often fraught with confusion given the variety of tests options used to evaluate a patient’s status
  • Hepatitis B surface antigen
    • Remains the gold standard of prenatal screening
    • Surface antigen is a protein marker of viral material present in the patient’s plasma
  • Hepatitis B surface antibody
    • Presence of the surface antibody indicates exposure at some point to either active virus or a component of the Hepatitis B vaccine
    • Implications of a positive Hepatitis B surface antibody report
      • For most patients born in the US, a positive hepatitis B surface antibody is suggestive of past immunologic response and not a current active infection
        • Confirmed with a negative result for hepatitis B surface antigen, which indicates no active viral material present in the plasma

Perinatal Transmission and Long Term Health Consequences

  • Perinatal transmission is associated with increased risk for long term health consequences including
    • Hepatocellular carcinoma
    • Liver cirrhosis and transplant
  • Neonatal management of infants born to mothers with HBV
    • Administer active and passive immunization with HBIG and HBV vaccination | Use of these modalities prevents 85% to 90% of HBV transmission | Still leaves 10% to 15% of children who will ultimately contract HBV
    • Due to serious potential health implications, targeted anti-viral therapy in pregnant women with high viral loads have been evaluated
      • Studies are reassuring that these treatments in the appropriate population reduce the risk for HBV transmission to the fetus/neonate while not conferring undue harm

Part 1: Testing

Testing Recommendations 

  • All pregnant women presenting for prenatal care should be tested for Hepatitis B surface antigen regardless of past history of infection or vaccination
  • Patients presenting for delivery should have repeat testing if high risk for infection including
    • More than one sex partner in past 6 months
    • Injection drug use
    • Known positive partner
    • Evaluation for STIs
  • Surface antigen testing should be performed prior to vaccination to avoid misinterpretation

Antigen Testing 

  • Antigen testing identifies presence of virus or viral particles
    • Surface antigen: Only present when Hepatitis B virus is present
    • Core antigen: A positive result provides evidence that not only are viral particles present but is also an indicator of infection

Antibody Testing 

  • Antibody testing detects elements of plasma that represent the body’s immune response to an exposure
    • Positive antibody result: Indicates that the patient’s immune system has been exposure to Hepatitis B antigen at some point
    • Hepatitis B vaccine:  Produced by injecting yeast with Hepatitis B RNA that then create the envelope protein we know as surface antigen
      • Therefore, the present of surface antibody is consistent with either prior infection or vaccination
  • To delineate infection from prior vaccination: Use core antibody
    • Viral core is not exposed to the immune system in vaccination | Therefore, the presence of core antibody is consistent with prior viral infection

Viral Load

  • Use viral load (HBV DNA) when Hepatitis B surface antigen is present
    • A high viral load of >6 to 8 log 10 copies/mL has been associated with a higher risk for vertical transmission in pregnant patients
    • If HBV DNA >200,000 IU/mL (7.6 log10 IU/mL): The American Association for the Study of Liver Diseases suggests antiviral therapy during pregnancy to further reduce perinatal HBV transmission
    • Once an active or chronic infection is diagnosed the patient should be referred to hepatology for further management

CDC HepB Test Interpretation Table 

Part 2: Pregnancy Implications

  • Pregnant patients with Hepatitis B infection
    • Usually uncomplicated course
    • HBV does not confer major risk of complication | Pregnancy does not hasten the course of the disease
  • Pregnancy is not a contraindication to hepatitis B vaccination
    • High risk women should be offered vaccination

Note: Patients with HBV are at increased risk for intrahepatic cholestasis of pregnancy and should be monitored for symptoms

Transmission Prevention 

Antenatal Period

  • Vertical transmission has been reported in the antenatal period although most transmission occurs during childbirth or in the neonatal period
  • There are no well documented interventions to prevent vertical transmission
  • ACOG recommends no alterations to obstetric management for women with HBV
    • Use of intrauterine monitoring and amniotomy when indicated
    • Cesarean delivery should be performed for routine obstetric indications

Neonatal Period

  • Neonatal acquisition of HBV is associated with higher rates of chronic infection and long-term sequelae
  • Neonatal standard of care
    • Treat all exposed neonates with HBIG
    • Begin Hepatitis B vaccine to prevent both acute and chronic acquisition
    • All household members should also be vaccinated against HBV

Part 3: Treatment during Pregnancy

  • Recommended that patients with high HBV viral loads be treated during pregnancy (based on RCT; Pan et al. NEJM, 2020)
  • Goal of treatment
    • Reduce viral burden and risk for vertical transmission
  • First line treatment: Tenofovir
    • Reverse transcriptase inhibitor that has been shown to be efficacious in treating HBV while conferring minimal side effects
    • Used in pregnancy with no increased risk to the neonate and not associated with increased risk for fetal/neonatal anatomic malformations
    • Order a viral load on any patient with a positive Hepatitis B surface antigen | If elevated refer to a hepatologist to manage the initiation of treatment

Note: Lamivudine has been evaluated as a treatment for HBV in pregnancy, given its well-known safety profile for the treatment of HIV in pregnancy |  However, using lamivudine as a single agent has resulted in the development of viral resistance and is no longer recommended as the first line treatment in pregnancy

Part 4: Counseling for The Postpartum Period

  • Prevention of infection following delivery is two-fold: Immediate prophylaxis and long-term vaccination
    • Hepatitis B immunoglobulin (HBIG): A newborn should receive HBIG within 12 hours after delivery
    • Hepatitis B vaccine series: Should also be initiated prior to newborn discharge
    • Additional practices such as immediate bathing is often employed 
  • Combination of HBIG and vaccination have reduced the risk for transmission at the time of birth to 5 to 15%
    • Employ these interventions if maternal status is unknown
  • The level of maternal HBV-DNA has been shown to be the greatest predictor of prophylaxis failure, therefore treatment of patients with high viral prior to pregnancy is key
  • Educate about the importance of hand hygiene and to recommend close household contacts to pursue vaccination if not already completed
  • Patient should continue their treatment for HBV if already initiated | Neonate should complete the Hepatitis B vaccine series
  • If patient not receiving treatment, encouraged follow up with their hepatologists or refer for long term care and management

The Wrap-Up

Next Steps for Patient in Our Case

  • Order the following
    • Hepatitis B surface antigen: To determine if she has an active HBV infection
    • HBV core antibody: Would help delineate if the patient has been vaccinated or had a prior infection
  • Results: If her HBV antigen results as negative she can be reassured that she is immune to HBV

Pregnant Women With HBV: Key Points

  • Pregnancy may be managed with routine prenatal care
  • Evaluate viral load
    • If elevated, referral to hepatology should be made for treatment with tenofovir
    • Obstetric management should remain unchanged for patients with HBV
    • Reserve cesarean delivery for obstetric indications
  • Care of neonates born to women with hepatitis B infection
    • Treat with HBIG and Hepatitis B vaccination
    • Additional counseling should be provided regarding vaccination for other close household contacts and proper hand hygiene to reduce risk of transmission

Learn More – Primary Sources

ACOG Practice Bulletin 86: Viral Hepatitis in Pregnancy

SMFM Consult Series #38: Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission

Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices

ACOG Practice Advisory: Hepatitis B Prevention

Screening for Hepatitis B Virus Infection in Pregnant Women: US Preventive Services Task Force Reaffirmation Recommendation Statement

Tenofovir to Prevent Hepatitis B Transmission in Mothers With High Viral Load (Pan et al. NEJM, 2016)

Commercial Support

This educational activity is supported by an independent educational grant from Gilead Sciences

Faculty Disclosures

Dr. Kohari reports that she has no relevant financial relationships to disclose

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